Autoimmune responses against photoreceptor antigens during retinal degeneration and their role in macrophage recruitment into retinas of RCS rats

J Neuroimmunol. 2013 Jan 15;254(1-2):91-100. doi: 10.1016/j.jneuroim.2012.10.007. Epub 2012 Oct 27.

Abstract

Autoimmunity may contribute to retinal degeneration. The studies examined the evolution of autoimmune responses against retina in naïve dystrophic RCS rats over the course of retinal degeneration. We showed that anti-retinal autoantibodies and T cells are generated in response to the availability of antigenic material released from dying photoreceptor cells during retinal degeneration but with distinctive activation trends. Passive transfer of anti-retinal antibodies enhanced disease progression by disrupting the BRB, upregulating MCP-1, attracting blood macrophages into retina, and augmenting apoptotic photoreceptor cell death. Our findings directly link anti-retinal autoantibodies to activated macrophage entry and their possible role in neurodegeneration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer / methods
  • Age Factors
  • Analysis of Variance
  • Animals
  • Antibodies / pharmacology
  • Antigens, CD / metabolism
  • Arrestin / immunology*
  • Autoimmunity / drug effects
  • Autoimmunity / physiology*
  • Cell Proliferation / drug effects
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Eye Proteins / immunology*
  • Female
  • In Situ Nick-End Labeling
  • Lymphocytes / drug effects
  • Macrophages / drug effects
  • Macrophages / pathology*
  • Male
  • Rats
  • Rats, Mutant Strains
  • Retina / drug effects
  • Retina / pathology*
  • Retinal Degeneration* / blood
  • Retinal Degeneration* / immunology
  • Retinal Degeneration* / pathology
  • Retinol-Binding Proteins / immunology*
  • Up-Regulation / drug effects
  • Up-Regulation / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies
  • Antigens, CD
  • Arrestin
  • Ccl2 protein, rat
  • Chemokine CCL2
  • Eye Proteins
  • Retinol-Binding Proteins
  • Vascular Endothelial Growth Factor A
  • interstitial retinol-binding protein